Nattokinase, a
serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that
nattokinase could reduce certain factors of blood clotting and
lipids that are associated with an increase risk for
cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of
nattokinase (2000 fibrinolysis units per
capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of
fibrinogen (P = .003),
factor VII (P < .001), and
factor VIII (P < .001), suggesting that the plasma levels of the 3
coagulation factors continuously declined during intake; also, the extents of decrease were similar between groups. After 2 months of administration,
fibrinogen,
factor VII, and
factor VIII decreased 9%, 14%, and 17%, respectively, for the Healthy Group; 7%, 13%, and 19%, respectively, for the Cardiovascular Group; and 10%, 7%, and 19%, respectively, for the Dialysis Group, whereas blood
lipids were unaffected by
nattokinase. No significant changes of
uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that
oral administration of
nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of
fibrinogen,
factor VII, and
factor VIII.